Hyperdiploid (47-50) acute lymphoblastic leukemia in children.

Among ploidy groups in childhood acute lymphoblastic leukemia (ALL), hyperdiploidy 47 to 50 is perhaps the least well known. From December 1979 to December 1990, we successfully studied banded karyotypes in 598 cases of newly diagnosed ALL, of which 86 (14.4%) had modal chromosome numbers of 47 to 50. In this group, the most frequently acquired numerical abnormalities were +21 (n = 34), +X (18), +8 (8), and +10 (7). The chromosomal regions most often affected by structural abnormalities were 1q (n = 13), 6q (12), 12p (18), and 19p (9). Analysis of event-free survival (EFS) for Studies X and XI among patients with hyperdiploid (47 to 50) ALL showed no significant differences in outcome according to the presence (n = 36) or absence (n = 35) of chromosomal translocations (P = .81) or the gain of specific chromosomes (P = .40). Patients with hyperdiploid (47 to 50) ALL treated in a contemporary program of multiagent chemotherapy had a significantly better outcome than did those in an earlier study using less intensive therapy (4-year EFS = 75% [95% confidence interval, 55% to 86%] v 41% [22% to 59%]; P = .006 by the logrank test). Our findings indicate that the adverse prognosis previously attributed to hyperdiploidy 47 to 50 improves significantly with more effective chemotherapy.     

Nasopharyngeal alveolar rhabdomyosarcoma expressing CD56: a mimicker of extranodal natural killer/T-cell lymphoma

Alveolar rhabdomyosarcoma (ARMS) is remarkably rare in adults older than 45 years. Histologically, the tumor is composed of blue round cells with frequent expression of CD56 in addition to myogenic markers. Recent studies of ARMS have shown two specific recurrent translocations: PAX3-FKHR [t(2;13)(q35;q14)] or PAX7-FKHR [t(1;13)(p36;q14)]. Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) occurs most frequently in the upper aerodigestive tract with a male preference in East Asia and Central and South Americas with neoplastic cells frequently expressing CD56. We report a 53-year-old Taiwanese man presenting with a nasopharyngeal mass, cervical lymphadenopathy, and multiple bone metastases. Histologically, the nasopharyngeal biopsy revealed diffuse sheets of small blue round tumor cells without obvious alveolar pattern, angioinvasion or tumor necrosis. An initial erroneous diagnosis of ENKTL was made due to CD56 expression using fresh tumor tissue with flow cytometric analysis and the patient was treated accordingly. Retrospective study showed that the tumor cells expressed CD56, desmin, and myogenin. Fluorescence in situ hybridization revealed that the tumor cells were positive for FKHR gene rearrangement, confirming the diagnosis of ARMS. Our case illustrates that a diagnosis of ENKTL based solely on CD56 expression can be misleading for a nasopharyngeal small blue round cell tumor. ARMS should be included as a differential diagnosis, and a correct diagnosis can be reached only after a high index of suspicion and a thorough histological examination with the aid of ancillary studies.     

Multiple telomeric associations of a trisomic whole q arm of chromosome 1 in a child with acute lymphoblastic leukemia

The results of cytogenetic analysis of bone marrow cells from a 13-year-old boy with acute lymphoblastic leukemia (ALL) are described. Initial analysis of aspirated bone marrow disclosed ALL FAB-L1 morphology, common (Ia+, cALLa+) immunophenotype and a complex abnormal karyotype. The majority of leukemic cells showed unbalanced translocations that resulted in complete trisomy of the long arm of chromosome #1 as the common denominator. The heterochromatic region of chromosome #1 (1qh) was associated with the telomeres of whole chromosomes #2, #13, and #16 in 28% of the 36 metaphases completely analyzed. Telomeric association is a very rare event and this is only the second known report of its occurrence associated with ALL wherein the 1qh region is attached to the telomeres of different chromosomes, resulting in trisomy of the whole 1q arm.     

Cholestasis in neonatal intensive care unit: incidence, aetiology and management

Aim:  Prevalence, aetiology, management and outcome of cholestasis were evaluated in infants admitted to neonatal intensive care unit (NICU).
Methods:  Medical records of all infants admitted to two Italian level III NICUs from January 2005 to August 2007 were retrospectively reviewed. The role of ursodeoxycholic acid (UDCA) therapy was also investigated.
Results:  Twenty-seven of 1289 enrolled infants developed cholestasis. In 25 infants, cholestasis had a multifactorial basis, while in two, no aetiology was found. UDCA did not significantly affect clinical and biochemical course of cholestasis. During a period of 12 months, eight cholestatic infants died, one underwent liver transplantation and 18 fully recovered.
Conclusion:  Infants admitted in NICU have a rate of cholestasis higher than that reported in the general population of live births; in most cases, cholestasis is associated to multiple risk factors and shows a favourable outcome. UDCA does not seem to affect clinical course of cholestasis in this setting.     

The effect of prebiotics in the management of neonatal hyperbilirubinaemia

Background:  Breast milk oligosaccharides such as galacto-oligosaccharides (scGOS) and fructo-oligosaccharides (lcFOS) can influence the intestinal microbial flora. The latter, in turn, can modulate several intestinal and extraintestinal functions, including bilirubin metabolism. Supplementing infant formula with a prebiotic mixture might then be a novel and safe intervention to manage mild neonatal hyperbilirubinaemia.
Aim:  To investigate the effect of dietary supplementation with prebiotics on moderate hyperbilirubinaemia in healthy, term infants.
Methods:  A prospective, double-blind, clinical trial was performed on seventy-six consecutive newborns who were randomly assigned to receive a formula containing 0.8 g/dL of a mixture from scGOS and lcFOS (ratio 9:1), or maltodextrines as placebo for 28 days. Bilirubin levels were determined by the transcutaneous bilirubin measurement within 2 h after birth (T1), at 24, 48 and 72 h and at 5, 7, 10 and 28 days of life. The number of stool per day was also recorded.
Results:  Neonates receiving prebiotics showed a larger number of stools over all the duration of dietary intervention compared to that of those on placebo (Repeated Measures ANOVA p < 0.001; day 28 3.4 ± 0.0.9 vs 1.7 ± 0.9, respectively; Dunn test p < 0.05). Neonates whose formula was supplemented with prebiotics showed a lower transcutaneous bilirubin that was statistically significant from 72 h of life (5.46 ± 1.6 vs 7.07 ± 2.49, post hoc Dunn test, p < 0.05) throughout the duration of the dietary intervention (day 28 2.41 ± 0.4 vs 2.85 ± 0.5, post hoc Dunn test, p < 0.05).
Conclusion:  The addition of prebiotics to standard infant diet might represent a novel strategy to help control neonatal hyperbilirubinaemia.     

A double-chamber rotating bioreactor for the development of tissue-engineered hollow organs: From concept to clinical trial

Cell and tissue engineering are now being translated into clinical organ replacement, offering alternatives to fight morbidity, organ shortages and ethico-social problems associated with allotransplantation. Central to the recent first successful use of stem cells to create an organ replacement in man was our development of a bioreactor environment. Critical design features were the abilities to drive the growth of two different cell types, to support 3D maturation, to maintain biomechanical and biological properties and to provide appropriate hydrodynamic stimuli and adequate mass transport. An analytical model was developed and applied to predict oxygen profiles in the bioreactor-cultured organ construct and in the culture media, comparing representative culture configurations and operating conditions. Autologous respiratory epithelial cells and mesenchymal stem cells (BMSCs, then differentiated into chondrocytes) were isolated, characterized and expanded. Both cell types were seeded and cultured onto a decellularized human donor tracheal matrix within the bioreactor. One year post-operatively, graft and patient are healthy, and biopsies confirm angiogenesis, viable epithelial cells and chondrocytes. Our rotating double-chamber bioreactor permits the efficient repopulation of a decellularized human matrix, a concept that can be applied clinically, as demonstrated by the successful tracheal transplantation.     

Possible relationships between headache–allodynia and nocturnal sleep breathing

Sleep and headache are linked in a bidirectional way. Breathing quality during sleep may be a possible link between them. The objective of this study were to evaluate the prevalence of headache—and of allodynia—in a population of subjects who underwent cardiopulmonary monitoring during sleep for presumed respiratory problems; to evaluate the possible relationships between the presence of headaches—and of allodynia—and respiratory parameters. We studied 181 subjects, 112 without headache (mean age 59.4 ± 13.1 years, 97 men and 15 women); 69 with history of headache (42 men and 27 women; 41 migraineurs and 28 with tension type headache). Headache diagnosis was made according to ICHD-II criteria. A semi-structured ad hoc questionnaire was used to evaluate the presence of allodynia. Full cardiopulmonary monitoring was performed by SOMNO check^® effort (WEINMANN) with SaO₂, T90 and AHI determination. Headache and headache-associated allodynia were particularly frequent in this population, suggesting a positive correlation between breathing problems during sleep and head pain, and allodynia. The observation that better respiratory parameters were found among headache sufferers with respect to those without headache, even in allodynic subjects, seems to reverse this point of view: headache and allodynia may possibly have an allostatic function preventing deep sleep and, in turn, avoiding prolonged apneas.

     

Is Obesity an Additional Risk Factor for Alcoholic Chronic Pancreatitis?

Background/Aims: Obesity is a known risk factor for severe acute pancreatitis (AP). Since alcoholic chronic pancreatitis (ACP) is closely linked to alcoholic AP, overweight before disease onset might impact on incidence and outcome of ACP, and represent an additional riskfactor for ACP. This issue has not been investigated, despite discussions on the ‘hypercaloric-high-fat’ hypothesis as an additional riskfactor for ACP for many years. Methods: The study is part of our prospective long-term study of a large, mixed, medical/surgical series of ACP patients. All cooperative patients were studied according to a protocol regarding clinical symptoms, physical status, routine laboratory tests, pancreatic function and pancreatic morphology (e.g. calcification) at yearly followups. Our study includes 227 ACP patients with recorded body mass index (BMI) before disease onset followed up on average for 18 years from chronic pancreatitis (CP) onset. Results: Males predominated (89.9%), age at onset averaged at 36 years, and exocrine insufficiency (97.4%) and calcification (88.1%) developed in virtually all patients. Surgery for B-type pain was performed in 57.7%, and death occurred in 62.8%. Overweight before disease onset was found in 54.2% (obesity in 15.0%) compared to 37.7% (3.1%) from a contemporary male control population. The highest BMI before disease onset did not impact on some major variables of ACP such as gender, age, progression of exocrine insufficiency, diabetes and calcification, and mortality from CP, except for a delayed progression rate of ACP indices in the surgical series. Conclusion: Overweight before disease onset appears to be another risk factor for ACP, supporting the ‘hypercaloric-high-fat’ hypothesis.